The development of inflammatory disease is characterized by infiltration of circulating blood cells, e.g., leukocytes, across the endothelium into the tissue. A number of key events occur in the endothelial cells that mediate this “gateway” function. The endothelial cells express receptors and chemokines that sequentially tether the leukocytes, activate them, cause them to tightly adhere, and extravasate between the endothelial cell junctions. This process is initiated by the production of early inflammatory mediators such as tumor necrosis factor (TNF).
The coordinated stimulation of expression of this series of receptors and chemokines is mediated by intracellular signaling molecules, including transcription factors, kinases and scaffolding proteins. These signaling molecules form a signaling cascade that may be a “master switch” for the development of inflammatory processes. Components of this cascade, such as NF-κB, are known. The analysis of genes that are differentially expressed in TNF-activated endothelium can help to identify components of the above-described “master switch” cascade.
The present invention provides the RET16 gene expressed in TNF-alpha-activated human endothelial cells, whose encoded product is regarded to function as a cell signaling molecule involved in the cell signaling cascade. Molecules which play a role in the cell signaling cascade are involved in cellular responses to inflammatory agents, such as cytokines, lymphokines, chemokines, leukotrienes and the like. Further, as a candidate cell signaling protein involved in the cell signaling cascade, RET16 is regarded to be involved in a variety of cell growth-related diseases or disorders.